tbuckley/cabot-search huggingface dataset:
Increased mortality risk for adults aged 25–44 years with long-term disability: A prospective cohort study with a 35-year follow-up of 30,080 individuals from 1984–2019 in the population-based HUNT study
Authors: Ellen Melbye Langballe, Gro Gujord Tangen, Bo Engdahl, Bjørn Heine Strand
Journal: The Lancet Regional Health - Europe (2022)

Differences in survival between groups may reflect avoidable and modifiable inequalities. This study examines the 35-year mortality risk for adults aged 25-44 years in the mid-1980s with disability due to vision, hearing, or motor impairment; physical illness; or mental health problems.This Norwegian study was based on data from the Trøndelag Health Study (HUNT1, 1984-86, and HUNT2, 1995-97) linked to tax-registry data for deaths before 15 November 2019. Mortality risk was estimated by Cox regression analysis adjusted for age and sex. Sensitivity analysis included the following possible mediators: education, work, living situation, body mass index, systolic blood pressure and smoking.Of the 30,080 HUNT1 participants aged 25-44 years, 5071 (16.9%) reported having disability. During the 35 years of follow-up, 1069 (21.1%) participants with disability and 3107 (12.4%) without disability died. Individuals with any type of disability had 62% higher mortality risk compared to those without a disability, adjusted by age and sex. The highest mortality risks were observed for disability due to severe motor impairment (HR=3.67, 95%CI=2.89-4.67) and severe mental health problems (HR=3.40, 95%CI=2.75-4.23) compared to those without these disabilities. Increased mortality risk was found for all the included disability types. The associations were somewhat mediated, especially by education, work and living situation.This study shows that among adults aged 25-44 years, the risk of death increases with disability of different types and severity levels, particularly for disability related to mental health problems or motor impairment.None.
Targeting of Nuclear Factor κB Pathways by Dehydroxymethylepoxyquinomicin, a Novel Inhibitor of Breast Carcinomas: Antitumor and Antiangiogenic Potential <i>In vivo</i>
Authors: Gaku Matsumoto, Jun-ichi Namekawa, Mariko Muta, Tadahiko Nakamura, Hiroko Bando, Kazumi Tohyama, Masakazu Toi, Kazuo Umezawa
Journal: Clinical Cancer Research (2005)

Abstract We previously designed and synthesized the new nuclear factor κB (NF-κB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) derived from the structure of the antibiotic epoxyquinomicin C. We looked into the effect of DHMEQ on cellular phenotypes and tumor growth in mice injected with human breast carcinoma cell line MDA-MB-231 or MCF-7. In estrogen-independent breast adenocarcinoma cell line MDA-MB-231, NF-κB is constitutively activated. The addition of DHMEQ (10 μg/mL) completely inhibited the activated NF-κB for at least 8 hours. On the other hand, NF-κB is not activated in estrogen-dependent MCF-7 cells. In this cell line, DHMEQ completely inhibited the tumor necrosis factor-α-induced activation of NF-κB. DHMEQ did not inhibit the degradation of IκB but inhibited the nuclear translocation of NF-κB by both p65/p50 and RelB/p52 pathways. MDA-MB-231 cells secrete interleukin (IL)-6 and IL-8 without stimulation, and DHMEQ decreased the secretion levels of both cytokines. When MDA-MB-231 or MCF-7 cells were stimulated by tumor necrosis factor-α, the inhibitory effects of DHMEQ were still maintained. I.p. administration of DHMEQ (thrice a week) significantly inhibited the tumor growth of MDA-MB-231 (12 mg/kg) or MCF-7 (4 mg/kg) in severe combined immunodeficiency mice. No toxicity was observed during the experiment, including the loss of body weight. An immunohistological study on resected MCF-7 tumors showed that DHMEQ inhibited angiogenesis and promoted apoptosis. Furthermore, in Adriamycin-resistant MCF-7 cells highly expressing multidrug resistance gene-1, DHMEQ also exhibited the above capability, including down-regulation of IL-8. Thus, DHMEQ might be a potent drug for the treatment of various breast carcinomas by inhibiting the NF-κB activity.
A dysregulated sebum–microbial metabolite–IL-33 axis initiates skin inflammation in atopic dermatitis
Authors: Zhuoqiong Qiu, Zhenlai Zhu, Xiaochun Liu, Baichao Chen, Huibin Yin, Chaoying Gu, Xiaokai Fang, Ronghui Zhu, Tianze Yu, Wenli Mi, Hong Zhou, Yufeng Zhou, Xu Yao, Wei Li
Journal: The Journal of Experimental Medicine (2022)

Microbial dysbiosis in the skin has been implicated in the pathogenesis of atopic dermatitis (AD); however, whether and how changes in the skin microbiome initiate skin inflammation, or vice versa, remains poorly understood. Here, we report that the levels of sebum and its microbial metabolite, propionate, were lower on the skin surface of AD patients compared with those of healthy individuals. Topical propionate application attenuated skin inflammation in mice with MC903-induced AD-like dermatitis by inhibiting IL-33 production in keratinocytes, an effect that was mediated through inhibition of HDAC and regulation of the AhR signaling pathway. Mice lacking sebum spontaneously developed AD-like dermatitis, which was improved by topical propionate application. A proof-of-concept clinical study further demonstrated the beneficial therapeutic effects of topical propionate application in AD patients. In summary, we have uncovered that the dysregulated sebum–microbial metabolite–IL-33 axis might play an initiating role in AD-related skin inflammation, thereby highlighting novel therapeutic strategies for the treatment of AD.
Lung cancer screening provides an opportunity for early diagnosis and treatment of interstitial lung disease
Authors: Richard J Hewitt, Emily C Bartlett, Rea Ganatra, Haroun Butt, Vasilis Kouranos, Felix Chua, Maria Kokosi, Philip L Molyneaux, Sujal R Desai, Athol U Wells, R Gisli Jenkins, Elisabetta A Renzoni, Samuel V Kemp, Anand Devaraj, Peter M George
Journal: Thorax (2022)

Interstitial lung abnormalities (ILA) can be incidentally detected in patients undergoing low-dose CT screening for lung cancer. In this retrospective study, we explore the downstream impact of ILA detection on interstitial lung disease (ILD) diagnosis and treatment. Using a targeted approach in a lung cancer screening programme, the rate of de novo ILD diagnosis was 1.5%. The extent of abnormality on CT and severity of lung function impairment, but not symptoms were the most important factors in differentiating ILA from ILD. Disease modifying therapies were commenced in 39% of ILD cases, the majority being antifibrotic therapy for idiopathic pulmonary fibrosis.
Cardiovascular Care in Brazil: Current Status, Challenges, and Opportunities
Authors: Otavio Berwanger, Karla Santo
Journal: Circulation (2022)

Brazil is the 5th largest country and the 6th most populous country in the world, with a population of >212 million people.In Brazil, noncommunicable diseases account for 72% of all deaths, of which about one-third are attributable to cardiovascular diseases (CVDs), the leading cause of death in the country. 1 In 2019, CVDs resulted in nearly 400 000 deaths, 1 the main causes being myocardial infarction (23.9% of CVD deaths), stroke (14.1% of CVD deaths), and heart failure (8.9% of CVD deaths). 2 The agestandardized mortality rates of these conditions have progressively declined by 17.5%, 42.7%, and 42.0%, respectively, since the early 2000s. 2 Heart failure represents the main cause of hospitalizations in Brazil, with >222 000 admissions in 2019. 1 The prevalence of CVD has increased by 26.8% in the past 3 decades.In 2019, the age-standardized CVD prevalence and incidence were 5454 and 475 per 100 000 inhabitants, respectively.
Clearance of multiple cutaneous warts by targeting a single lesion: A randomized comparative evaluation of mild local hyperthermia versus cryotherapy
Authors: Rui-Qun Qi, Junfeng Zhou, Bihuan Xiao, Honghui Xu, Shuai Qiao, Peiyao Zhu, Lixin Xia, Yang Yang, Li Zhang, Hongwei Yan, Congcong He, Yuzhe Sun, Xueli Niu, Yuqing Zhang, Lingyu Fu, Xiuli Wang, Hong-Duo Chen, Shanshan Li, Xing-Hua Gao
Journal: Journal of the American Academy of Dermatology (2022)
p53 Activation Paradoxically Causes Liver Cancer
Authors: Michelle C. Barton, Guillermina Lozano
Journal: Cancer Research (2022)

Activation of p53 regulates a transcriptional program that can cause cell cycle arrest, senescence, apoptosis, and ferroptosis, which are potent tumor suppressive mechanisms. Unexpectedly, Makino and colleagues show in this issue of Cancer Research that the constitutive activation of p53 in murine hepatocytes leads to tumor development. Detailed analyses indicate that p53 activation leads to loss of hepatocytes, increased expression of chemokines and humoral factors, and expansion of the hepatic progenitor cell population. These progenitor cells are highly proliferative, show chromosomal instability, and eventually transform. In chronic liver disease in humans, activation of p53 is associated with increased liver cancer development. This study highlights the complexity and non-cell autonomous nature of the physiologic p53 response. See related article by Makino et al., p. 2860
Association of Decrease in Body Mass Index With Reduced Incidence and Progression of the Structural Defects of Knee Osteoarthritis: A Prospective <scp>Multi‐Cohort</scp> Study
Authors: Zubeyir Salis, Blanca Gallego, Tuan V. Nguyen, Amanda Sainsbury
Journal: Arthritis & Rheumatology (2022)

Objective To define the association between change in body mass index (BMI) and the incidence and progression of the structural defects of knee osteoarthritis as assessed by radiography. Methods Radiographic analyses of knees at baseline and at 4–5 years of follow‐up were obtained from the following 3 independent cohort studies: the Osteoarthritis Initiative (OAI) study, the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study. Logistic regression analyses using generalized estimating equations, with clustering of both knees within individuals, were used to investigate the association between change in BMI from baseline to 4–5 years of follow‐up and the incidence and progression of knee osteoarthritis. Results A total of 9,683 knees (from 5,774 participants) in an “incidence cohort” and 6,075 knees (from 3,988 participants) in a “progression cohort” were investigated. Change in BMI was positively associated with both the incidence and progression of the structural defects of knee osteoarthritis. The adjusted odds ratio (OR) for osteoarthritis incidence was 1.05 (95% confidence interval [95% CI] 1.02–1.09), and the adjusted OR for osteoarthritis progression was 1.05 (95% CI 1.01–1.09). Change in BMI was also positively associated with degeneration (i.e., narrowing) of the joint space and with degeneration of the femoral and tibial surfaces (as indicated by osteophytes) on the medial but not on the lateral side of the knee. Conclusion A decrease in BMI was independently associated with lower odds of incidence and progression of the structural defects of knee osteoarthritis and could be a component in preventing the onset or worsening of knee osteoarthritis.
In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis
Authors: Shi-Xiong Chen, Ji Zhang, Fengfeng Xue, Wei Liu, Yichen Kuang, Bingxin Gu, Shaoli Song, Hangrong Chen
Journal: Bioactive Materials (2022)

Though the development of the diverse hypoxia-activated prodrugs (HAPs) has made great progresses in the last several decades, current cancer therapy based on HAPs still suffers many obstacles, e.g., poor therapeutic outcome owing to hard deep reaching to hypoxic region, and the occurrence of metastasis due to hypoxia. Inspired by engineered niches, a novel functional chitosan polymer (CS-FTP) is synthesized for construction of a hydrogel-based bio-niche (CS-FTP-gel) in aiming at remodeling tumor hypoxic microenvironment. The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor, in which a HAP (i.e., AQ4N) could be physically encapsulated, resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy. Furthermore, Pazopanib (PAZ) conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation, eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model. This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.
Associations Between Low Serum Urate, Body Composition, and Mortality
Authors: Joshua F. Baker, David R. Weber, Tuhina Neogi, Michael D. George, Jin Long, Lindsay N. Helget, Bryant R. England, Ted R. Mikuls
Journal: Arthritis & Rheumatology (2022)

Objective Controversy remains as to whether low serum urate or uric acid (UA) levels contribute to adverse outcomes. We evaluated the relation between low serum UA levels and sarcopenia and assessed whether sarcopenia confounds associations between these low levels and mortality. Methods We utilized data from the National Health and Nutrition Examination Survey (1999–2006). Participants with available whole‐body dual x‐ray absorptiometry body composition measurements and serum UA concentrations were included. Body composition assessments included body mass index (BMI), waist circumference, maximum lifetime BMI, and age‐, sex‐, and race‐specific appendicular lean mass index (ALMI) and fat mass index (FMI) Z scores. We also calculated Z scores for ALMI relative to FMI (ALMI FMI ). We evaluated associations between serum UA levels and body composition using logistic regression and assessed associations between serum UA levels and mortality before and after adjusting for differences in body composition using Cox proportional hazards regression. Results Among the 13,979 participants, low serum UA concentrations (&lt;2.5 mg/dl in women, &lt;3.5 mg/dl in men) were associated with low lean mass (ALMI and ALMI FMI Z scores), underweight BMI (&lt;18.5 kg/m 2 ), and higher rates of weight loss. The proportion of patients with low ALMI Z scores was 29% in the low serum UA group and 16% in the normal serum UA group ( P = 0.001). Low serum UA levels were associated with increased mortality before we adjusted for body composition (hazard ratio 1.61 [95% confidence interval 1.14–2.28]; P = 0.008) but was attenuated and not significant after adjustment for body composition and weight loss (hazard ratio 1.30 [95% confidence interval 0.92–1.85], P = 0.13). Conclusion Sarcopenia and weight loss are more common among patients with low serum UA concentrations. Differences in body composition may help to explain associations between low levels of serum UA and higher mortality.
Reinfection and Risk Behaviors After Treatment of Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy
Authors: Jason Grebely, Gregory J. Dore, Frederick L. Altice, Brian Conway, Alain H. Litwin, Brianna L. Norton, Olav Dalgard, Edward J. Gane, Oren Shibolet, Ronald Nahass, Anne F. Luetkemeyer, Cheng-Yuan Peng, David Iser, Isaias Noel Gendrano, Michelle M. Kelly, Peggy Hwang, Ernest Asante-Appiah, Barbara A. Haber, Eliav Barr, Michael N. Robertson, Heather Platt
Journal: Annals of Internal Medicine (2022)

Background: Hepatitis C virus (HCV) reinfection after successful treatment may reduce the benefits of cure among people who inject drugs. Objective: To evaluate the rate of HCV reinfection for 3 years after successful treatment among people receiving opioid agonist therapy (OAT). Design: A 3-year, long-term, extension study of persons enrolled in the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) study (ClinicalTrials.gov: NCT02105688). Setting: 55 clinical trial sites in 13 countries. Patients: Aged 18 years and older with chronic HCV infection with genotypes 1, 4, or 6 receiving stable OAT. Intervention: No treatments were administered. Measurements: Serum samples were assessed for HCV reinfection. Urine drug screening was performed. Results: Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. The rate of HCV reinfection was 1.7 [95% CI, 0.8 to 3.0] per 100 person-years; 604 person-years of follow-up). A higher rate of reinfection was seen among people with recent injecting drug use (1.9 [95% CI, 0.5 to 4.8] per 100 person-years; 212 person-years). Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up. Limitations: Participants were required to be 80% adherent to OAT at baseline and may represent a population with higher stability and lower risk for HCV reinfection. Rate of reinfection may be underestimated because all participants did not continue in the long-term extension study; whether participants who discontinued were at higher risk for reinfection is unknown. Conclusion: Reinfection with HCV was low but was highest in the first 24 weeks after treatment completion and among people with ongoing injecting drug use and needle–syringe sharing. Primary Funding Source: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition)
Authors: Ying-Hui Jin, Xian-Tao Zeng, Tong-Zu Liu, Zhi-Ming Bai, Zhong-Ling Dou, De-Gang Ding, Zhi-Lu Fan, Ping Han, Yi-Ran Huang, Xing Huang, Ming Li, Xiao-Dong Li, Yi-Ning Li, Xu-Hui Li, Chao-Zhao Liang, Jiu-Min Liu, Hong-Shun Ma, Juan Qi, Jia-Qi Shi, Jian Wang, De-Lin Wang, Zhi-Ping Wang, Yun-Yun Wang, Yong-Bo Wang, Qiang Wei, Hai-Bo Xia, Jin-Chun Xing, Si-Yu Yan, Xue-Pei Zhang, Guo-You Zheng, Nian-Zeng Xing, Da-Lin He, Xing-Huan Wang
Journal: Military Medical Research (2022)

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.
Examining the Relationship between Climate Change and Vibriosis in the United States: Projected Health and Economic Impacts for the 21st Century
Authors: Megan Sheahan, Caitlin A. Gould, James E. Neumann, Patrick L. Kinney, Sandra Hoffmann, Charles Fant, Xinyue Wang, Michael Kolian
Journal: Environmental Health Perspectives (2022)

Background: This paper represents, to our knowledge, the first national-level (United States) estimate of the economic impacts of vibriosis cases as exacerbated by climate change. Vibriosis is an illness contracted through food- and waterborne exposures to various Vibrio species (e.g., nonV. cholerae O1 and O139 serotypes) found in estuarine and marine environments, including within aquatic life, such as shellfish and finfish. Objectives: The objective of this study was to project climate-induced changes in vibriosis and associated economic impacts in the United States related to changes in sea surface temperatures (SSTs). Methods: For our analysis to identify climate links to vibriosis incidence, we constructed three logistic regression models by Vibrio species, using vibriosis data sourced from the Cholera and Other Vibrio Illness Surveillance system and historical SSTs. We relied on previous estimates of the cost-per-case of vibriosis to estimate future total annual medical costs, lost income from productivity loss, and mortality-related indirect costs throughout the United States. We separately reported results for V. parahaemolyticus, V. vulnificus, V. alginolyticus, and “V. spp.,” given the different associated health burden of each. Results: By 2090, increases in SST are estimated to result in a 51% increase in cases annually relative to the baseline era (centered on 1995) under Representative Concentration Pathway (RCP) 4.5, and a 108% increase under RCP8.5. The cost of these illnesses is projected to reach $5.2 billion annually under RCP4.5, and $7.3 billion annually under RCP8.5, relative to $2.2 billion in the baseline (2018 U.S. dollars), equivalent to 140% and 234% increases respectively. Discussion: Vibriosis incidence is likely to increase in the United States under moderate and unmitigated climate change scenarios through increases in SST, resulting in a substantial burden of morbidity and mortality, and costing billions of dollars. These costs are mostly attributable to deaths, primarily from exposure to V. vulnificus. Evidence suggests that other factors, including sea surface salinity, may contribute to further increases in vibriosis cases in some regions of the United States and should also be investigated. https://doi.org/10.1289/EHP9999a
TOX deficiency facilitates the differentiation of IL-17A-producing γδ T cells to drive autoimmune hepatitis
Authors: Qifeng He, Yijun Lu, Wenfang Tian, Runqiu Jiang, Weiwei Yu, Yong Liu, Meiling Sun, Fei Wang, Haitian Zhang, Ning Wu, Zhongjun Dong, Beicheng Sun
Journal: Cellular and Molecular Immunology (2022)